A P300 event-related potential, the so-called "decision wave", is generated when attention is drawn to infrequent environmental events. The P300 is widely used in clinical and basic psychological research to draw inferences about human cognition. Therefore, the neural origin of the P300 is of considerable interest to cognitive neuroscientists and clinicians. Studies in our laboratory have shown that unilateral lesions in prefrontal or temporal-parietal association cortex can reduce or abolish components of the auditory P300. A variety of evidence, including intracranial recordings from hippocampal formation, suggests an important role of limbic structures in P300 generation. Neuroanatomical studies in primates have documented reciprocal connections through which prefrontal and temporal-parietal cortex could modulate hippocampal function. The scalp P300 may index the engagement of this association cortex-hippocampal circuit, which is activated during the detection and encoding of biologically significant stimuli. A series of studies is proposed to investigate the contributions of association cortex and hippocampus to P300 generation. Groups of patients with focal infarctions of prefrontal or posterior association cortex, or infarctions of the posterior hippocampus will be studied. Parallel detection experiments with graded levels of difficulty will be performed in auditory, visual and somatosensory modalities. High resolution MRI neuroimaging will be used to reconstruct lesion extent in all patients, and to evaluate possible modality-specific elements of P300 generator circuits. Concurrent analyses of reaction times and response accuracy will be used to characterize the cognitive concomitants of the P300 abnormalities. The proposed research plan is designed to provide systematic data on the neural and behavioral substrates of the P300.